This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction This study is examining the effect of cognitive-behavioral therapy on the neural bases of emotional reactivity and regulation in adults diagnosed with social anxiety disorder. Specific Aims The overall goal of this proposal is to elucidate the neural bases of emotional reactivity and cognitive regulation in social phobia (SP), and to identify the neural mechanisms underlying therapeutic change associated with cognitive-behavioral therapy (CBT). Basic research has examined emotional reactivity and cognitive regulation in healthy controls (HC) [10, 11], but this research has not yet delineated the mechanisms underlying emotion regulation in individuals with SP. Clinical research has shown that CBT is an effective treatment for many individuals with SP [12], but mechanisms of change and predictors of therapeutic response have not yet been well described. To integrate basic and clinical literatures, we use a translational framework that views emotion regulation in terms of interactions between ventral emotion-generative brain regions and dorsal emotion-regulatory brain regions. Within this framework, we propose to examine the neural substrates of emotional reactivity and cognitive regulation in HC and in participants with generalized SP pre- and post-CBT. Our proposed studies address 3 aims: Aim 1 examines the neural substrates of emotional reactivity and cognitive regulation in SP versus HC;Aim 2 identifies mechanisms of change by examining SP participants pre- and post-CBT;Aim 3 assesses predictors of longer-term treatment responses to CBT. The broad, long-term objective of this translational research program is to contribute to advances in theory and clinical interventions that will improve the psychological health of individuals suffering from SP. Methods and Materials We intend to assess 120 adults (ages 21-55 years). Of these, 80 will meet DSM-IV [83] criteria for a primary diagnosis of current generalized social phobia (SP) at Time 1. The other 40 participants will be non-psychiatric healthy controls (HC) each matched to an SP on age, sex, education, ethnicity, and handedness. This sample size will provide sufficient statistical power to examine (a) SP vs. HC at pre-CBT Time 1 (Aim 1), (b) pre- to post-CBT changes via within- and between-subjects effects (Aim 2), and (c) predictors of longer-term response to CBT treatment (Aim 3). All participants will undergo diagnostic interviewing, behavioral assessment, a battery of questionnaires, computer task, and fMRI task to assess facets of anxiety, emotional reactivity and regulation.